Research Article

L-Carvone from Mentha spicata L. Leaves Suppresses Oxidative Stress and Hypertrophy in the Isoproterenol-Induced Rat Model of Cardiac Hypertrophy

Abstract

The effect of L-Carvone (a natural monoterpene from Mentha spicata L., leaves) in cardiac hypertrophy caused by isoproterenol administration was investigated. Male rats (Wistar) were divided into five groups: Control, diseased, diseased rats with losartan, diseased rats with low-dose L-Carvone, and high-dose L-Carvone. Rats were injected with isoproterenol (5 mg/kg) for 30 days to induce cardiac hypertrophy. Then, simultaneously with Losartan (15 mg/kg), L-Carvone was administered orally at a dosage of 25 mg/kg (low dose) and 100 mg/kg (high dose) treatment. The cardioprotective effect of L-Carvone was evaluated by examining the heart morphometric indices, and ECG analyses. Chronic isoproterenol administration resulted in changes in morphometric indices of the heart, ECG tracings, biochemical parameters such as tissue glucose, proteins, lipid profiles, serum cardiac markers, antioxidants, and histopathological integrity of the heart tissue. When compared with the isoproterenol group, L-Carvone administrated for 30 days ameliorated all these changes in rats significantly (p < 0.05). L-Carvone adequately averted chronic cardiac hypertrophy, most probably through its antioxidant potential.

Erkens R, Kramer CM, Luckstadt W, Panknin C, Krause L, et al., Left ventricular diastolic dysfunction in Nrf2 knock out mice is associated with cardiac hypertrophy, decreased expression of SERCA2a, and preserved endothelial function. Free Radic Biol Med 2015;89:906-917.

Younis NS, Abduldaium MS, Mohamed ME. Protective effect of geraniol on oxidative, inflammatory and apoptotic alterations in isoproterenol-induced cardiotoxicity: Role of the Keap1/Nrf2/HO-1 and PI3K/Akt/mTOR pathways. Antioxidants 2020;9:977.

Rajasekaran NS, Varadharaj S, Khanderao GD, Davidson CJ, Kanna S, et al. Sustained activation of nuclear erythroid 2-related factor 2/antioxidant response element signaling promotes reductive stress in the human mutant protein aggregation cardiomyopathy in mice. Antioxid Redox Signal 2011;14:957-996.

Yan LJ. Pathogenesis of chronic hyperglycemia: from reductive stress to oxidative stress. J Diabetes Res 2014;2014:137919

Nagarajan A, VA D. Antihypertrophic Effect of Menthol from Mentha x piperita - Cardiac Hypertrophy Review. Nat Prod J 2023;13:e290422204272 .

Wang Y, Zhen D, Fu D, Fu Y, Zhang X, et al. 1, 8-cineole attenuates cardiac hypertrophy in heart failure by inhibiting the miR-206-3p/SERP1 pathway. Phytomedicine 2021;91:153672.

Meeran MN, Jagadeesh GS, Selvaraj P. Thymol, a dietary monoterpene phenol abrogates mitochondrial dysfunction in β-adrenergic agonist induced myocardial infarcted rats by inhibiting oxidative stress. Chem Biol Interact 2016;244:159-168.

Bouyahya A, Mechchate H, Benali T, Ghchime R, Charfi S, et al. Health benefits and pharmacological properties of carvone. Biomol 2021;11:1803.

Elmastas M, Dermirtas I, Isildak O, Aboul‐Enein, H. Antioxidant activity of S-carvone isolated from spearmint (Mentha Spicata L. Fam Lamiaceae). J Liq chromatogr Relat Technol 2006;29: 1465-1475.

Rajeshwari T, Raja B. Antioxidant and free radical scavenging effect of D-carvone in hypertensive rats. Int Lett Nat Sci 2015;35:6-12.

Silva GBA, Souza DS, Menezes-Filho JER, Silva-Neto JA, Cruz JS, et al. Vasconcelos CML. (-)-Carvone Modulates intracellular calcium signaling with antiarrhythmic action in rat hearts. Arq Bras Cardiol 2022;119:294-304.

Alsanea S, Liu D. BITC and S-carvone restrain high-fat diet-induced obesity and ameliorate hepatic steatosis and insulin resistance. Pharm Res 2017;34:2241-2249.

Khudhair AM, Abed AL Ani. Primary phytochemical identification and some biochemical parameters study of ethanolic extract of Mentha spicata leaves in mice. J Chem Pharm Res 2016; 8:818-822.

Alelign T, Chalchisa D, Fekadu N, Solomon D, Sisay T, et al. Evaluation of acute and sub-acute toxicity of selected traditional antiurolithiatic medicinal plant extracts in wistar albino rats. Toxicol Rep 2020;7:1356-1365.

Ennis IL, Escudero EM, Console GM, Camihort G, Dumm CG, et al. Regression of isoproterenol-induced cardiac hypertrophy by Na+/H+ exchanger inhibition. Hypertension 2003; 41:1324-1329.

Zhao L, Chen H, Chen J, Yu M, Ni Y, et al. Losartan reduced connexin43 expression in left ventricular myocardium of spontaneously hypertensive rats. J Zhejiang Uni Sci B 2008;9;448-454.

Muruganathan U, Srinivasan S, Indumathi D. Antihyperglycemic effect of carvone: effect on the levels of glycoprotein components in streptozotocin-induced diabetic rats. J Acute Dis 2013; 2:310-315.

Nagarajan A, Doss VA. L-carvone attenuates myocardial injury and dyslipidemia in rats with isoproterenol-induced cardiac hypertrophy. Asian Pac J Trop Biomed 2023;13:17-25.

Sanchez-Campos S, Tunon MJ, Gonzalez P, Gonzalez-Gallego J. Oxidative stress and changes in liver antioxidant enzymes induced by experimental dicroceliosis in hamsters. Parasitol Res 1999;85:468-474.

Mahajan L, Saxena S, Sarma PU. Phosphorus compounds: Their discovery in the biological world. Indian J Clin Biochem 2018;33:243-245.

Vander Vries J. Two methods for the determination of glycogen in the liver. Biochem J 1954; 57:410-416.

Solanki A, Agarwal P. Comprehensive analysis of changes in clinically significant divalent serum cation levels during automated plateletpheresis in healthy donors in a tertiary care center in North India. Asian J Transfus Sci 2015;9:124-128.

Moraes FD, Rossi PA, Figueiredo JSL, Venturini FP, Cortella LRX, et al. Metabolic responses of channel catfish (Ictalurus punctatus) exposed to phenol and post-exposure recovery. An Acad Bras Cienc 2016;88:865-875.

Ahmadi F, Lee WH, Oh YK, Park K, Kwak WS. Fruit and vegetable discards preserved with sodium metabisulfite as a high-moisture ingredient in total mixed ration for ruminants: Effect on in vitro ruminal fermentation and in vivo metabolism. Asian Australas J Anim Sci 2020;33:446-455.

Swain HS, Das BK, Upadhyay A, Ramteke MH, Kumar V, et al. Stocking density-mediated stress modulates growth attributes in cage-reared Labeo rohita (Hamilton) using a multifarious biomarker approach. Sci Rep 2022;12:9869.

Stocks J, Dormandy TL. The autoxidation of human red cell lipids induced by hydrogen peroxide. Br J Haematol 1971;20:95-111.

Beauchamp C, Fridovich I. Anal Biochem 1971;44:276-287.

Sinha AK. Colorimetric Assay of catalase. Analyst Biochem 1972;47:389-394

Ellman GL. Tissue sulfhydryl groups. Arch Biochem Biophys 1959;82:70-77.

Habig WH, Pabst MJ, Jakoby WB. Glutathione S-transferases. The first enzymatic step in mercapturic acid formation. J Biol Chem 1974;249:7130-7139.

Beutler E: Red cell metabolism: In A Manual of Biochemical Methods, 3rd ed. Grune and Straton, New York 1984; pp 71-73.

Omaye ST, David Turnbull J, Sauberlich HE. Selected methods for the determination of ascorbic acid in animal cells, tissues, and fluids. Vitamins and Coenzymes Part D, 1979;62:3-11.

Jargar JG, Hattiwale SH, Das S, Dhundasi SA, Das KK. A modified simple method for determination of serum α-tocopherol (vitamin E). JBCPP 2012;23:45-48.

Moron M, Depierre J, Mannervik B. Levels of glutathione, glutathione reductase and glutathione S-transferase activities in rat lung and liver. Biochim Biophys Acta Gen Subj 1979; 582:67-78.

Wong F. Cirrhotic cardiomyopathy. Hepatol Int 2009;3:294.

Meeran MFN, Jagadeesh GS, Selvaraj P. Thymol attenuates inflammation in isoproterenol-induced myocardial infarcted rats by inhibiting the release of lysosomal enzymes and downregulating the expressions of proinflammatory cytokines. Eur J Pharmacol 2015;754:153-161.

Ferrari CKB, Torres EAFS. Biochemical pharmacology of functional foods and prevention of chronic diseases of aging. Biomed Pharmacother 2003;57:251-260.

Santos MRV, Moreira FV, Fraga BP, Souza DP de, Bonjardim LR, et al. Cardiovascular effects of monoterpenes: a review. Rev Bras Farmacogn 2011;21:764-771.

Muruganathan U, Srinivasan S. Beneficial effect of carvone, a dietary monoterpene ameliorates hyperglycemia by regulating the key enzyme activities of carbohydrate metabolism in streptozotocin-induced diabetic rats. Biomed Pharmacother 2016;84:1558-1567.

Mesquita TRR, de Jesus ICG, dos Santos JF, de Almeida GKM, de Vasconcelos CML, et al. Cardioprotective action of Ginkgo biloba extract against sustained b adrenergic stimulation occurs via activation of M2/NO pathway. Front Pharmacol 2017;8:1-13.

Chen K, Wu T, Zhang R, Song H. Effects of swertiamarin on TGF-b1/Smad signaling pathway in rats with carbon tetrachloride-induced liver fibrosis. Int J Clin Exp Med 2017;10:2316-2325.

Al-Rasheed NM, Al-Oteibi MM, Al-Manee RZ, Al-Shareef NM, Hasan IH, et al. Simvastatin prevents isoproterenol-induced cardiac hypertrophy through modulation of the JAK/STAT pathway. Drug Des Dev Ther 2015;9:3217-3229.

Zhang J, Knapton A, Lipshultz SE, Weaver JL, Herman EH. Isoproterenol-induced cardiotoxicity in Sprague-Dawley rats correlation of reversible and irreversible myocardial injury with release of cardiac troponin T and roles of iNOS in myocardial injury. Toxicol Pathol 2008; 36:277-288.

Chang GR, Chen WK, Hou PH, Mao FC. Isoproterenol exacerbates hyperglycemia and modulates chromium distribution in mice fed with a high-fat diet. J Trace Elem Med Biol 2017; 44:315-321.

Deshaies Y, LeBlanc J, Willemot J. Studies on protein metabolism during isoproterenol-induced cardiac hypertrophy. Recent Adv Stud Card Struct Metab 1975;8:387-395.

Summermatter S, Santos G, Schindler JP, Handschin C. Skeletal muscle PGC-1a controls whole-body lactate homeostasis through estrogen-related receptor a-dependent activation of LDH B and repression of LDH A. PNAS 2013;10:8738-8743.

Meeran MFN, Azimullah S, Al Ahbabi MM, Jha NK, Lakshmanan VK, et al. Nootkatone, a dietary fragrant bioactive compound, attenuates dyslipidemia and intramyocardial lipid accumulation and favorably alters lipid metabolism in a rat model of myocardial injury: an in vivo and in vitro study. Molecules 2020;25:5656.

Meeran MFN, Jagadeesh GS, Selvaraj P. Thymol attenuates altered lipid metabolism in β-adrenergic agonist myocardial infarcted rats by inhibiting tachycardia, altered electrocardiogram, apoptosis, and cardiac hypertrophy. J Funct Foods 2015;14:51-62.

Anandan R, Chatterjee NS, Sivakumar R, Mathew S, Asha KK, et al. Dietary chitosan supplementation ameliorates isoproterenol-induced aberrations in membrane-bound ATPases and mineral status of rat myocardium. Biol Trace Elem Res 2015;167:103-109.

Dhivya V, Priya LB, Chirayil HT, Sathiskumar S, Huang CY, et al. Piperine modulates isoproterenol-induced myocardial ischemia through antioxidant and anti-dyslipidemic effects in male Wistar rats. Biomed Pharmacother 2017;87:705-713.

Meeran MFN, Laham F, Al-Taee H, Azimullah S, Ojha S. Protective effects of α-bisabolol on altered hemodynamics, lipid peroxidation, and nonenzymatic antioxidants in isoproterenol-induced myocardial infarction: In vivo and in vitro evidence. J Biochem Mol Toxicol 2018;32: e22200.

Jemai H, Sayadi S. Heart histopathology and oxidative features in diabetic rats and protective effects of Oleuropein. Adv Biosci Biotechnol 2015;6:383-389.

Wu T, Li J, Li Y, Song H. Antioxidant and hepatoprotective effect of swertiamarin on carbon tetrachloride-induced hepatotoxicity via the Nrf2/HO-1 pathway. Cell Physiol Biochem 2017;41: 2242-2254.

Files
IssueVol 9, No 1, 2024 QRcode
SectionResearch Article(s)
DOI https://doi.org/10.18502/tim.v9i1.15086
Keywords
M. spicata L. L-Carvone Antioxidant Cardioprotective Antihypertrophic

Rights and permissions
Creative Commons License This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
How to Cite
1.
Nagarajan A, VA D. L-Carvone from Mentha spicata L. Leaves Suppresses Oxidative Stress and Hypertrophy in the Isoproterenol-Induced Rat Model of Cardiac Hypertrophy. Trad Integr Med. 2024;9(1):24-35.